Inhibition of human astrocyte and microglia neurotoxicity by calcium channel blockers

We examined the effects of L-type calcium channel blockers (CCBs) on toxicity exerted by activated human astrocytes and microglia towards SH-SY5Y human neuronal cells. The CCBs nimodipine (NDP) and verapamil (VPM) both significantly suppressed toxic secretions from human astrocytes and astrocytoma U-373 MG cells that were induced by interferon (IFN)-gamma. NDP also inhibited neurotoxic secretions of human microglia and monocytic THP-1 cells that were induced by the combination of lipopolysaccharide and IFN-gamma. In human astrocytes, both NDP and VPM reduced IFN-gamma-induced phosphorylation of signal transducer and activator of transcription (STAT) 3. They also inhibited the astrocytic production of IFN-gamma-inducible T cell alpha chemoattractant (I-TAC). These results suggest that CCBs attenuate IFN-gamma-induced neurotoxicity of human astrocytes through inhibition of the STAT3 signaling pathway. L-type CCBs, especially NDP, might be a useful treatment option for a broad spectrum of neurodegenerative diseases, including Alzheimer disease, where the pathology is believed to be exacerbated by neurotoxic glial activation. (C) 2012 Elsevier Ltd. All rights reserved.